OpenOnco v0.1.2 · 2026-04-30
OpenOnco · DIS-BREAST · BIO-HRR-PANEL (ESCAT IIA)
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Treatment plan — DIS-BREAST
PLAN-BMA-ATM_GERMLINE_BREAST-V1 · v1 · 2026-05-04
Patient
BMA-ATM_GERMLINE_BREAST · Algorithm: ALGO-BREAST-1L

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks
BiomarkerVariantESCATEvidenceClinical significanceDrugsSources
BIO-HRR-PANELATM germline pathogenicIIAATM germline pathogenic confers ~2× lifetime breast-cancer risk; no PARPi indication (TBCRC-048 ATM cohort showed minimal activity). Standard breast- cancer therapy by ER/HER2 status. ESCAT IIA (predisposition) / OncoKB Level 3A. Avoid radiotherapy in homozygous/biallelic ATM (radiosensitivity).standard breast therapy by HR/HER2
enhanced screening (annual MRI)
  • SRC-NCCN-BREAST-2025
  • SRC-ESMO-BREAST-METASTATIC-2024
BIO-HRR-PANELBARD1 germline pathogenicIIA
  • SRC-CIVIC: Level A (Supports, Sensitivity/Response)
BARD1 germline pathogenic confers moderate breast-cancer risk (~2-3×). BARD1 forms heterodimer with BRCA1 → biological HR deficiency. Limited clinical PARPi data; off-label consideration. ESCAT IIA / OncoKB Level 3A.standard breast therapy
olaparib off-label (HRR rationale)
  • SRC-NCCN-BREAST-2025
  • SRC-ESMO-BREAST-METASTATIC-2024
BIO-HRR-PANELBRIP1 germline pathogenicIIIA
  • SRC-CIVIC: Level A (Supports, Sensitivity/Response)
BRIP1 germline pathogenic and breast cancer: weak/uncertain risk association (NCCN does not currently recommend enhanced breast surveillance based on BRIP1 alone). No PARPi indication. ESCAT IIIA / OncoKB Level 3B.standard breast therapy by subtype
  • SRC-NCCN-BREAST-2025
BIO-HRR-PANELCHEK2 germline pathogenicIIA
  • SRC-NCCN-BREAST-2025
  • SRC-ESMO-BREAST-METASTATIC-2024
Evidence cited from clinical guidelines; per-source evidence levels not yet structured. See Phase-2-of-CIViC-pivot for re-cite roadmap.
CHEK2 germline pathogenic (e.g. 1100delC) confers ~2× breast-cancer risk; no PARPi activity demonstrated (TBCRC-048 CHEK2 cohort minimal response). Standard HR/HER2-directed therapy. ESCAT IIA (predisposition) / OncoKB Level 3A.standard breast therapy by subtype
enhanced screening (annual MRI from age 40)
  • SRC-NCCN-BREAST-2025
  • SRC-ESMO-BREAST-METASTATIC-2024
BIO-HRR-PANELPALB2 germline pathogenicIIA
  • SRC-CIVIC: Level A (Supports, Sensitivity/Response)
PALB2 germline pathogenic confers BRCA-like breast risk (~50% lifetime). Olaparib activity reported in PALB2-mutated breast (Tung TBCRC-048: ORR ~82% in HER2-negative metastatic, n=11) but PARPi labels in breast remain BRCA- only. NCCN lists PALB2 as a PARPi-eligible mutation off-label. ESCAT IIA / OncoKB Level 3A.olaparib (off-label per NCCN, TBCRC-048 evidence)
talazoparib (off-label)
platinum-based chemo (TNBC)
  • SRC-NCCN-BREAST-2025
  • SRC-ESMO-BREAST-METASTATIC-2024
BIO-HRR-PANELRAD51B germline pathogenicIIIA
  • SRC-CIVIC: Level A (Supports, Sensitivity/Response)
RAD51B germline pathogenic in breast: moderate-risk allele (~RR 2-4 for RAD51C/D, less established for RAD51B). No PARPi label; off-label consideration in HRD context. ESCAT IIB-IIIA / OncoKB Level 3B.standard breast therapy
PARPi off-label (HRD-positive context)
  • SRC-NCCN-BREAST-2025
BIO-HRR-PANELRAD51C germline pathogenicIIB
  • SRC-NCCN-BREAST-2025
Evidence cited from clinical guidelines; per-source evidence levels not yet structured. See Phase-2-of-CIViC-pivot for re-cite roadmap.
RAD51C germline pathogenic in breast: moderate-risk allele (~RR 2-4 for RAD51C/D, less established for RAD51B). No PARPi label; off-label consideration in HRD context. ESCAT IIB-IIIA / OncoKB Level 3B.standard breast therapy
PARPi off-label (HRD-positive context)
  • SRC-NCCN-BREAST-2025
BIO-HRR-PANELRAD51D germline pathogenicIIB
  • SRC-CIVIC: Level A (Supports, Sensitivity/Response)
RAD51D germline pathogenic in breast: moderate-risk allele (~RR 2-4 for RAD51C/D, less established for RAD51B). No PARPi label; off-label consideration in HRD context. ESCAT IIB-IIIA / OncoKB Level 3B.standard breast therapy
PARPi off-label (HRD-positive context)
  • SRC-NCCN-BREAST-2025
BIO-HRR-PANELRAD54L germline pathogenicIIIA
  • SRC-CIVIC: Level A (Supports, Sensitivity/Response)
RAD54L germline variants: rare; HR-pathway gene with limited clinical evidence. Included in some HRR panels but no labeled indication. ESCAT IIIA / OncoKB Level 4.standard therapy
PARPi off-label (HRD context only)
  • SRC-NCCN-BREAST-2025
  • SRC-ESMO-BREAST-METASTATIC-2024

Treatment options (7 tracks)

Standard plan
★ DEFAULT
Indication
IND-BREAST-HR-POS-MET-1L-CDKI
Regimen
AI + ribociclib (HR+/HER2- metastatic 1L; OS-validated)
Drugs + NSZU
  • Letrozole (DRUG-LETROZOLE) 2.5 mg PO daily · Continuous · PO ✓ NSZU covered
  • Ribociclib (DRUG-RIBOCICLIB) 600 mg PO daily, days 1-21 of 28-day cycle · 21 days on, 7 days off · PO ⚠ NSZU — not for this indication
Supportive care
SUP-BONE-HEALTH-PROSTATE
Reason
Engine default per algorithm ALGO-BREAST-1L: {'step': 5, 'outcome': False, 'branch': {'result': 'IND-BREAST-HR-POS-MET-1L-CDKI'}, 'fired_red_flags': [], 'winner_red_flag': None}
Standard plan
Indication
IND-BREAST-HER2-POS-EARLY-NEOADJUVANT
Regimen
TCHP — docetaxel + carboplatin + trastuzumab + pertuzumab (HER2+ neoadjuvant)
Drugs + NSZU
  • Docetaxel (DRUG-DOCETAXEL) 75 mg/m² IV · Day 1 of 21-day cycle x 6 cycles · IV ✓ NSZU covered
  • Carboplatin (DRUG-CARBOPLATIN) AUC 6 IV · Day 1 of 21-day cycle x 6 cycles · IV ⚠ NSZU — not for this indication
  • Trastuzumab (DRUG-TRASTUZUMAB) 8 mg/kg IV loading, 6 mg/kg IV maintenance · Day 1 of 21-day cycle · IV ✓ NSZU covered
  • Pertuzumab (DRUG-PERTUZUMAB) 840 mg IV loading, 420 mg IV maintenance · Day 1 of 21-day cycle · IV ✓ NSZU covered
Supportive care
SUP-BONE-HEALTH-PROSTATE, SUP-G-CSF-PRIMARY-PROPHYLAXIS-PROSTATE
Reason
Alternative track presented for HCP consideration
Standard plan
Indication
IND-BREAST-HER2-POS-MET-1L-THP
Regimen
THP — docetaxel + trastuzumab + pertuzumab (HER2+ metastatic 1L)
Drugs + NSZU
  • Docetaxel (DRUG-DOCETAXEL) 75-100 mg/m² IV · Day 1 of 21-day cycle x 6-8 cycles, then HP maintenance · IV ✓ NSZU covered
  • Trastuzumab (DRUG-TRASTUZUMAB) 8 mg/kg loading, 6 mg/kg maintenance IV · Day 1 of 21-day cycle, continuous until progression · IV ✓ NSZU covered
  • Pertuzumab (DRUG-PERTUZUMAB) 840 mg loading, 420 mg maintenance IV · Day 1 of 21-day cycle, continuous until progression · IV ✓ NSZU covered
Supportive care
SUP-BONE-HEALTH-PROSTATE
Reason
Alternative track presented for HCP consideration
Standard plan
Indication
IND-BREAST-HER2-POS-MET-2L-TDXD
Regimen
T-DXd monotherapy (HER2+ metastatic 2L+, also HER2-low metastatic)
Drugs + NSZU
  • Trastuzumab deruxtecan (T-DXd) (DRUG-TRASTUZUMAB-DERUXTECAN) 5.4 mg/kg IV · Day 1 of 21-day cycle, continuous until progression · IV ✓ NSZU covered
Supportive care
SUP-BONE-HEALTH-PROSTATE
Reason
Alternative track presented for HCP consideration
Standard plan
Indication
IND-BREAST-TNBC-EARLY-NEOADJUVANT
Regimen
Pembrolizumab + chemo (TNBC neoadjuvant)
Drugs + NSZU
  • Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3 weeks · Days 1 of cycles 1-8 (4 cycles each phase) · IV ⚠ NSZU — not for this indication
  • Paclitaxel (DRUG-PACLITAXEL) 80 mg/m² IV weekly · Cycles 1-4 (12 weekly doses) · IV ✓ NSZU covered
  • Carboplatin (DRUG-CARBOPLATIN) AUC 5 IV · Cycles 1-4 q3 weeks (or weekly AUC 1.5) · IV ⚠ NSZU — not for this indication
  • Doxorubicin (DRUG-DOXORUBICIN) 60 mg/m² IV · Cycles 5-8 q3 weeks · IV ✓ NSZU covered
  • Cyclophosphamide (DRUG-CYCLOPHOSPHAMIDE) 600 mg/m² IV · Cycles 5-8 q3 weeks · IV ✓ NSZU covered
Supportive care
SUP-G-CSF-PRIMARY-PROPHYLAXIS-PROSTATE, SUP-BONE-HEALTH-PROSTATE
Reason
Alternative track presented for HCP consideration
Standard plan
Indication
IND-BREAST-BRCA-POS-MET-PARPI
Regimen
Olaparib monotherapy (BRCA-mutant HER2- breast: metastatic OR adjuvant high-risk early)
Drugs + NSZU
  • Olaparib (DRUG-OLAPARIB) 300 mg PO BID continuous · Until progression (metastatic) or 1 year (OlympiA adjuvant) · PO ⚠ NSZU — not for this indication
Supportive care
SUP-BONE-HEALTH-PROSTATE
Reason
Alternative track presented for HCP consideration
IND-BREAST-TNBC-METASTATIC-1L-PEMBRO-CHEMO
Indication
IND-BREAST-TNBC-METASTATIC-1L-PEMBRO-CHEMO
Regimen
Reason
Alternative track presented for HCP consideration

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks
IDNamePriorityCategoryWhere to orderNeeded for
TEST-CECT-CAPCECT chest/abdomen/pelvisCriticalimagingstandard
TEST-ER-PR-IHCER + PR immunohistochemistry on tumorCriticalCSD Lab ✓ (code TBC)standard
TEST-HER2-IHC-FISHHER2 IHC + reflex FISH on tumorCriticalCSD Lab ✓ (code TBC)standard
TEST-GERMLINE-BRCA-PANELGermline BRCA1/2 + HRR panel sequencingStandardCSD Lab: M089standard
TEST-PIK3CA-NGSPIK3CA mutation testing (tumor or ctDNA)StandardCSD Lab: M065desired (standard)

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track
  • Age ≥75 + ECOG ≥2 + significant comorbidity — anthracycline + dose-dense regimens poorly tolerated; consider TC, weekly paclitaxel, single-agent endocrine, or trastuzumab + chemo of reduced intensity.RF-BREAST-FRAILTY-AGE
  • Cardiac dysfunction (LVEF <50%) — anthracycline + trastuzumab/pertuzumab + T-DM1/T-DXd all carry cardiotoxicity risk; baseline echo + serial monitoring required.RF-BREAST-ORGAN-DYSFUNCTION

CONTRA-AGGRESSIVE

Hard contraindications to escalation

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · AI + ribociclib (HR+/HER2- met
28-day cycles × Continuous until progression

Standard plan

Induction · TCHP — docetaxel + carboplatin
21-day cycles × 6 (then surgery → adjuvant trastuzumab + pertuzumab to complete 1 year HER2-targeted therapy; T-DM1 if residual disease)

Standard plan

Induction · THP — docetaxel + trastuzumab
21-day cycles × Docetaxel × 6-8; HP continues until progression

Standard plan

Induction · T-DXd monotherapy (HER2+ metas
21-day cycles × Continuous until progression or unacceptable toxicity

Standard plan

Induction · Pembrolizumab + chemo (TNBC ne
21-day cycles × 8 (paclitaxel/carbo+pembro phase 1-4, then AC+pembro phase 5-8)

Standard plan

Induction · Olaparib monotherapy (BRCA-mut
28-day cycles × Adjuvant: 12; Metastatic: continuous until progression

MDT brief

Data quality

  • Unevaluated RedFlags: RF-BREAST-AKT1-E17K-ACTIONABLE, RF-BREAST-AKT1-E17K-CAPIVASERTIB-CANDIDATE, RF-BREAST-BRCA-GERMLINE-ACTIONABLE, RF-BREAST-CDH1-LOBULAR-CANDIDATE, RF-BREAST-ESR1-MUT-ACTIONABLE, RF-BREAST-ESR1-Y537S-D538G-CANDIDATE, RF-BREAST-FRAILTY-AGE, RF-BREAST-HER2-AMP-ACTIONABLE, RF-BREAST-HER2-LOW-ACTIONABLE, RF-BREAST-HER2-ULTRALOW-CANDIDATE, RF-BREAST-HIGH-RISK-BIOLOGY, RF-BREAST-INFECTION-SCREENING, RF-BREAST-ORGAN-DYSFUNCTION, RF-BREAST-OVARIAN-HRD-ASSAY-DISTINCTION, RF-BREAST-PIK3CA-COALT-INAVOLISIB-CANDIDATE, RF-BREAST-PIK3CA-MUT-ACTIONABLE, RF-BREAST-TRANSFORMATION-PROGRESSION, RF-PAN-ATM-CHEK2-CDK12-PARPI-CANDIDATE, RF-PAN-BRCA-SOMATIC-PARPI-CANDIDATE, RF-PAN-PALB2-PARPI-CANDIDATE

Skill catalog (0/16 activated in this plan)

All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).
Specialistskill_idVersionLast reviewedSign-offsDomain
Cellular therapy specialist (CAR-T)cellular_therapy_specialistv0.1.02026-04-250cellular_therapy
Clinical pharmacistclinical_pharmacistv0.1.02026-04-250clinical_pharmacy
Hematologist / oncohematologisthematologistv0.1.02026-04-250hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)hematopathologistv0.1.02026-04-250hematopathology
Infectious disease / hepatologyinfectious_disease_hepatologyv0.1.02026-04-250infectious_diseases
Medical oncologist (solid-tumor chemotherapist)medical_oncologistv0.1.02026-04-250solid_oncology
Molecular geneticist / molecular oncologistmolecular_geneticistv0.1.02026-04-250molecular_oncology
Palliative carepalliative_carev0.1.02026-04-250palliative_care
Pathologist (general)pathologistv0.1.02026-04-250pathology
Primary care / family physicianprimary_carev0.1.02026-04-250primary_care
Psycho-oncologistpsychologistv0.1.02026-04-250psychosocial
Radiation oncologistradiation_oncologistv0.1.02026-04-250radiation_oncology
Radiologistradiologistv0.1.02026-04-250diagnostic_imaging
Social worker / case managersocial_worker_case_managerv0.1.02026-04-250psychosocial
Surgical oncologistsurgical_oncologistv0.1.02026-04-250surgical_oncology
Transplant specialist (BMT)transplant_specialistv0.1.02026-04-250cellular_therapy

Sources cited

Experimental options (clinical trials)

Third plan track — open-enrollment trials from ClinicalTrials.gov. Render-time metadata; engine selection is not affected by this block (CHARTER §8.3). Last synced: 2026-05-04.
NCTTitlePhaseStatusSponsorUAEligibility (excerpt)
NCT06903468Novel Cavity Marking Technique in Breast Cancer Patients Undergoing Breast Conservation Surgery With Oncoplastic Reconstruction for the Delivery of Adjuvant Radiotherapy and Accuracy of Recommended Re-excisionsNARECRUITINGUniversity of Florida
NCT02422641Prospective Evaluation Of High-Dose Systemic Methotrexate In Patients With Breast Cancer And Leptomeningeal MetastasisPHASE2RECRUITINGWake Forest University Health Sciences
NCT06781281NabPE With or Without Serplulimab for Early-stage HR+/HER2- Breast Cancer.N/ARECRUITINGHenan Cancer Hospital
NCT05919108Neoadjuvant Neratinib in Stage I-III HER2-Mutated Lobular Breast CancersPHASE2RECRUITINGVanderbilt-Ingram Cancer Center
NCT04437160Adjuvant Chemotherapy for Triple Negative Breast Cancer Patients With Residual Disease After Neoadjuvant ChemotherapyPHASE2RECRUITINGChinese Academy of Medical Sciences
NCT03827317HERPET- A Novel PET Imaging Study of HER2 in Breast CancerNARECRUITINGImperial College London
NCT05196087Non-Invasive Artificial Intelligence-Based Platform MonIToring Program (NIP IT!)N/ARECRUITINGUniversity Health Network, Toronto
NCT04891068BRE-04: Window of Opportunity Trial of Preoperative Low Dose Azacitidine in High-Risk Early Stage Breast CancerPHASE2RECRUITINGUniversity of Illinois at Chicago
NCT04553770Trastuzumab Deruxtecan Alone or in Combination With Anastrozole for the Treatment of Early Stage HER2 Low, Hormone Receptor Positive Breast CancerPHASE2RECRUITINGJonsson Comprehensive Cancer Center
NCT04368702CONFIRM: Magnetic Resonance Guided Radiation TherapyNARECRUITINGBrigham and Women's Hospital

Verify recruitment status directly with the trial site. ctgov data can lag behind current UA-site status.

Option availability in Ukraine

Per-track UA registration · NSZU · cost · access pathway. Render-time metadata; engine selection does not depend on these fields (CHARTER §8.3).
OptionUA registrationNSZUCost orientationAccess pathway
Standard plan
AI + ribociclib (HR+/HER2- metastatic 1L; OS-validated) (REG-AI-RIBOCICLIB)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary
Standard plan
TCHP — docetaxel + carboplatin + trastuzumab + pertuzumab (HER2+ neoadjuvant) (REG-TCHP-NEOADJUVANT)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary
Standard plan
THP — docetaxel + trastuzumab + pertuzumab (HER2+ metastatic 1L) (REG-THP-METASTATIC)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary
Standard plan
T-DXd monotherapy (HER2+ metastatic 2L+, also HER2-low metastatic) (REG-TDXD-METASTATIC)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary
Standard plan
Pembrolizumab + chemo (TNBC neoadjuvant) (REG-PEMBRO-CHEMO-TNBC-NEOADJUVANT)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary
Standard plan
Olaparib monotherapy (BRCA-mutant HER2- breast: metastatic OR adjuvant high-risk early) (REG-OLAPARIB-BREAST)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary
IND-BREAST-TNBC-METASTATIC-1L-PEMBRO-CHEMO
No regimen components on this track — availability unknown
— unknown— unknown₴-? — verify pathwaynot recorded
Trial · NCT06903468
Novel Cavity Marking Technique in Breast Cancer Patients Undergoing Breast Conservation Surgery With Oncoplastic Reconstruction for the Delivery of Adjuvant Radiotherapy and Accuracy of Recommended Re-excisions
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT02422641
Prospective Evaluation Of High-Dose Systemic Methotrexate In Patients With Breast Cancer And Leptomeningeal Metastasis
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT06781281
NabPE With or Without Serplulimab for Early-stage HR+/HER2- Breast Cancer.
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT05919108
Neoadjuvant Neratinib in Stage I-III HER2-Mutated Lobular Breast Cancers
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT04437160
Adjuvant Chemotherapy for Triple Negative Breast Cancer Patients With Residual Disease After Neoadjuvant Chemotherapy
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT03827317
HERPET- A Novel PET Imaging Study of HER2 in Breast Cancer
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT05196087
Non-Invasive Artificial Intelligence-Based Platform MonIToring Program (NIP IT!)
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT04891068
BRE-04: Window of Opportunity Trial of Preoperative Low Dose Azacitidine in High-Risk Early Stage Breast Cancer
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT04553770
Trastuzumab Deruxtecan Alone or in Combination With Anastrozole for the Treatment of Early Stage HER2 Low, Hormone Receptor Positive Breast Cancer
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT04368702
CONFIRM: Magnetic Resonance Guided Radiation Therapy
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-04.